The aim of this research program involves elucidation of the ion permeability mechanisms expressed by primary cells cultured from the embryonic mammalian CNS, from endocrine pituitary and from immune tissues. These mechanisms are considered critical in the physiology and diverse functions of the various cellular phenotypes. Specific lines of investigation include projects on embryonic CNS neurons cultured from spinal and supraspinal regions, clonal and primary pituitary cells, and clonal and primary effector lymphocytes as well as their tumor targets. Electrophysiological measurements of excitability are made in membrane patches or in whole cells, using either low-resistance patch-clamp pipettes or high-resistance microelectrodes for recording. The different assay techniques provide complementary data for characterizing the membrane and cytoplasmic mechanisms underlying ion conductances in these cells. Principal observations this year include the following: 1) simultaneous whole-cell patch-type electrical recordings from cultured GABAergic and target hippocampal neurons in functional synaptic contact; 2) quantitative analysis of GABA-mediated synaptic signals; 3) structure-activity-study of requirements for steroid modulation of GABA receptor-coupled Cl- conductance: active steroids occur naturally as metabolites of certain hormones and may amplify inhibitory signals throughout the CNS; 4) discovery of a relatively novel depolarizing conductance that may be proximal to epileptogenic activity; 5) transient-type K+ channels in clonal pituitary cells have the same elementary conductance as delayed-type K+ channels but distinct pharmacologies; 6) prolactin and growth-hormone cells sorted from the adult rat pituitary express excitable membrane properties in culture; 7) interleukin-2 induces delayed-type anionic conductance mechanisms in putative killer-type lymphocytes; 8) leukoregulin triggers the transient appearance of depolarizing ion channel activity.